Acute <i>Trem2</i> reduction triggers increased microglial phagocytosis, slowing amyloid deposition in mice
Kathleen M. Schoch, Lubov Ezerskiy, Michaela M. Morhaus, Riley N. Bannon, Andrew D. Sauerbeck, Mark Shabsovich, Paymaan Jafar‐Nejad, Frank Rigo, Timothy M. Miller
Abstract
Significance Alzheimer’s disease (AD) remains a significant health burden within the aging population and currently lacks therapies that effectively target pathological events to halt the development or progression of AD. The gene TREM2 appears to influence abnormal protein accumulations in AD through the brain’s immune cells; however, it is not clear if and when TREM2 might be targeted in disease to limit pathology or the immune response. We used antisense oligonucleotides (ASOs) to reduce Trem2 levels in the mouse brain at specific times in disease and investigated amyloid protein accumulations, microglial responses, and genetic signatures. ASO-mediated Trem2 lowering during late-stage disease reduced amyloid pathology, which may have been triggered by an acute activation of microglia to engulf and clear amyloid deposits.